title: Cytosine methylation changes in enhancer regions of core pro-fibrotic genes characterize kidney fibrosis development.
abstract: BACKGROUND
  One in eleven people is affected by chronic kidney disease, a condition characterized by kidney fibrosis and progressive loss of kidney function. Epidemiological studies indicate that adverse intrauterine and postnatal environments have a long-lasting role in chronic kidney disease development. Epigenetic information represents a plausible carrier for mediating this programming effect. Here we demonstrate that genome-wide cytosine methylation patterns of healthy and chronic kidney disease tubule samples obtained from patients show significant differences.
  
  
  RESULTS
  We identify differentially methylated regions and validate these in a large replication dataset. The differentially methylated regions are rarely observed on promoters, but mostly overlap with putative enhancer regions, and they are enriched in consensus binding sequences for important renal transcription factors. This indicates their importance in gene expression regulation. A core set of genes that are known to be related to kidney fibrosis, including genes encoding collagens, show cytosine methylation changes correlating with downstream transcript levels.
  
  
  CONCLUSIONS
  Our report raises the possibility that epigenetic dysregulation plays a role in chronic kidney disease development via influencing core pro-fibrotic pathways and can aid the development of novel biomarkers and future therapeutics.
authors.forename: Yi-An
authors.initials: YA
authors.lastname: Ko
authors.forename: Davoud
authors.initials: D
authors.lastname: Mohtat
authors.forename: Masako
authors.initials: M
authors.lastname: Suzuki
authors.forename: Ae Seo Deok
authors.initials: AS
authors.lastname: Park
authors.forename: Maria Concepcion
authors.initials: MC
authors.lastname: Izquierdo
authors.forename: Sang Youb
authors.initials: SY
authors.lastname: Han
authors.forename: Hyun Mi
authors.initials: HM
authors.lastname: Kang
authors.forename: Han
authors.initials: H
authors.lastname: Si
authors.forename: Thomas
authors.initials: T
authors.lastname: Hostetter
authors.forename: James M
authors.initials: JM
authors.lastname: Pullman
authors.forename: Melissa
authors.initials: M
authors.lastname: Fazzari
authors.forename: Amit
authors.initials: A
authors.lastname: Verma
authors.forename: Deyou
authors.initials: D
authors.lastname: Zheng
authors.forename: John M
authors.initials: JM
authors.lastname: Greally
authors.forename: Katalin
authors.initials: K
authors.lastname: Susztak
mesh_terms: D000368:Aged; D001483:Base Sequence; D001665:Binding Sites; D016022:Case-Control Studies; D016000:Cluster Analysis; D003596:Cytosine / Q000378:metabolism*; D019175:DNA Methylation; D004742:Enhancer Elements, Genetic; D005355:Fibrosis; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D053263:Gene Regulatory Networks; D006801:Humans; D007668:Kidney / Q000378:metabolism* / Q000473:pathology*; D008875:Middle Aged; D059372:Nucleotide Motifs; D056510:Position-Specific Scoring Matrices; D051436:Renal Insufficiency, Chronic / Q000235:genetics / Q000473:pathology; D015203:Reproducibility of Results; D014157:Transcription Factors; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D014157:Transcription Factors; D003596:Cytosine